Conduct Disorder (CD) is a psychiatric diagnosis of children and adolescents who persistently violate basic rights of others and major age-appropriate societal norms. These youths engage in repeated, major acting-out. This is the diagnosis most frequently associated with child and adolescent referrals for mental health treatment. Between 1/3 and 1/2 of these youths will grow into adults with serious Antisocial Personality Disorder (ASP). The condition tends to run in families with substance abuse and ASP, and there appears to be a genetic component in its etiology. CD should be of major interest to NICA, since youths with CD often have associated Psychoactive Substance Use Disorder (PSUD). Major Depressive Disorder and abnormalities of EEG or evoked potentials also occur often among CD youths. Although, many psychological and pharmacological treatments are used in CD, few have demonstrated efficacy, even in the short term, and none have been shown effective in the long term. This is a major problem for which more research clearly is needed The Addiction Research and Treatment Service of the CU School of Medicine, conducts a treatment program for adolescent boys with comorbid PSUD and aggressive CD. These youths have had intensive (mostly polydrug) drug abuse, many arrests, group home or detention placements, and extensive abuse and neglect. There is reason to believe that many of them will mature into the next generation of criminal street addicts. This project has 9 specific aims. (1) We will increase our CO treatment capacity, approximately doubling our census and increasing turnover through our residential beds. (2) The capacity increase will result from enhanced treatment, with the addition of new post-residential emancipation, intensive day-evening, and outpatient treatment components. (3) We further will enhance treatment by providing extremely detailed psychological, medical, and neurophysiologic evaluations at admission, with continuing assessments through treatment. (4) We will provide the first detailed research into the admission psychological and biological characteristics of a large group of drug-abusing CD youth. (5) We will identify admission characteristics which predict course in treatment and (6) post-treatment outcome, We will assess in open and double-blind studies the efficacy of (7) imipramine for Major Depressive Disorder, (8) lithium for aggressiveness, and (9) carbamazepine for a combination of aggressiveness and EEG abnormalities, in selected subsets of drug-abusing CD youth, carefully assessing treatment effects on drug-abuse and other outcome measures. We know of no other university-based drug-abuse research program conducting a treatment facility for this severely neglected and very important population of drug abusers. We believe that this proposed program can make major contributions to the understanding and treatment of these patients.